1. Technical Field
The document relates to methods and materials for generating T cells (e.g., antigen-specific CD4+ T cells). For example, this document relates to using nested MHC class II epitopes as vaccines to generate activated CD4+ T cells in vivo or as reagents to generate activated CD4+ T cells ex vivo.
2. Background Information
Adoptive transfer of large numbers of antigen-specific T cells has a therapeutic potential for being used to regress tumors or eliminate infection. Effective adoptive T cell therapy appears to require antigen-specificity as activated non-specific T cells do not appear to be very effective. The generation of antigen-specific T cells typically takes weeks to months and results in weak antigen-specific responses, T cell exhaustion, senescence, and loss of polyclonality. Strategies are being examined to improve antigen-specific T cell generation. One of the more often employed strategies is to supplement cell culture media with T cell activating cytokines that have recently been made available by better production capabilities. Another strategy used, although less easily employed, is the use of tetramers to isolate antigen-specific T cells for culture. Yet another is to immunize in vivo and harvest lymph node cells for eventual ex vivo expansion.